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Senior - Heme-Onc > Lecture 3 - Macrocytic Anemia > Flashcards

Lecture 3 - Macrocytic Anemia Flashcards

1
Q

MCV >100?

A

Macrocytic anemia

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2
Q

Basic mechanism of anemia? (Causes)

A

RBC disruption

  • dietary deficiency
  • abnormal metabolism of B12/folate
  • ineffective erythropoiesis
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3
Q

If MCV > 100 you need to test for?

A

B 12

Folate

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4
Q

MCV >100 with
- Low vitamin B12

What may cause this?

A

Megaloblastic anemai (pernicious anemia)

Think:

  • dietary deficiency
  • GI disease
  • Post-gastrectomy
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5
Q

MCV >100 with:
- low folate?

What may cause this?

A

Megaloblastic anemia

Dietary deficiency
GI disease

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6
Q

MCV > 100 with:

- normal B12 and folate?

A

Liver diseases
Myelodysplastic syndrome
Reticulocytosis

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7
Q

Common causes of macrocytosis.

Its a long list, dont memorize it

A

DNA metabolism

  • B12
  • folate
  • Drugs
    • Hydroxuriea
    • methotrexate

Shift to immature or stressed RBC

  • reticulocytosis
  • aplastic anemia

Primary bone marrow disorder
- myelodysplastic syndromes

Liver abnormalities

  • liver disease
  • hypothyroidism
  • hyperlipidemia

MOA ukn
- ETOH

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8
Q

Pt has macrocytic anemia with normal B12 and folate

You find Hypersegmented neutrophils on peripheral smear

A

Strongly suggest megalobastic anemia

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9
Q

Pt has macrocytic anemia with normal B12 and folate

No nutritional or drug induced cause.
Look at how high the MCV is

100:

> 105:

A

100

  • hypothyroidism,
  • pregnancy,
  • liver disease,
  • ETOH

> 105: bone marrow d/o (MDS)

  • late megalobastic anemia
  • pernicious anemia
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10
Q

Common social causes of macrocytic?

A

ETOH

Drugs

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11
Q

Macrocytic anemia iwth microcytes and macrocytes on peripheral smear

A

Pt has coexisting condition probably:

  • IDA
  • Thalassemia
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12
Q

What is megaloblastic anemia?

A

A type of macrocytic anemia

A group of blood disorders that share common morphological characteristics (large, atypical)

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13
Q

MC cause of megalobastic anemia?

A

B12 and folic acid deficiency (usually intake problem, looking at you jake)

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14
Q

What do folate and B12 do for the body?

A

Purine synthesis and subsequent DNA synthesis

  • leads to abnormal erythropoiesis
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15
Q

What is the biggest concern for untreated B12 deficiency?

A

Neuropsychiatric symptoms (late sign)

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16
Q

B12 deficiency essentials of diagnosis?

A
  • MCV > 100
  • Macro-ovalocyutes and hypersegmented neutrophils
  • serum B12 low
    • <170g/mL (low)
    • 200-300 (borderline)
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17
Q

If B12 is 200-300 order?

A

MMA (methylmalonic acid)

Homocysteine

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18
Q

Why High MMA with low b12?

A

B12 is a cofactor in conversion of methylmalonyl-CoA succinyl-CoA in the mitochondria

Thus low B12 leads to accumulation of MMA

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19
Q

Where does B12 come from?

A

Animals

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20
Q

How much B12 do we store and use? How long can we go w/ out it?

A

Liver stores 2000-5000mcg

Daily use is 3-5mcg

You have approx 3 yrs till you need more

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21
Q

Cause of B12 deficiency?

A

Strict Vegans

Abdominal surgery

Rare causes

  • fish tapeworm
  • severe crohn’s
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22
Q

Clinical findings of B12 deficiency?

A 
Megaloblastic anemia
- Fatigue, palor, malaise, SOB
HCT < 10-15%
Changes in mucosal cells 
- glossitis, Gi complaints

Neuropsychiatric symptoms

23
Q

Describe neuropsychatric symptoms

A

Peripheral nerves first -> paresthesias
Balance problems -> ataxia
Cerebral function leading to dementia (late)

24
Q

What are the 2 steps required for the body to absorb b12?

A
  1. Hydrochloric acid separates b12 from carier protein

2. B12 combines w IF for absorption in TERMINAL ILEUM

25
Q

Pts with Pernicious Anemia have? (Causes)

A

Antibody to IF or parietal cells

Parietal cells are the site of production of IF

26
Q

What does folate (b9) do in the body?

A

It is a co-factor in cellular reactions, but does not participate in methylmalonic acid metabolism (MMA)
- so normal MMA on labs

27
Q

Sources of B9?

A

Fruits (citrus)

Green leafy vegetables

28
Q

What is entherohepatic recirculation?

A

One of 2 methods for absorption of B9 (folate)

The B9 rides the bile train back into the intestine

The other method is normal absorption

29
Q

Storage and use of B9?

A

Store about 5000 mcg

You use lots of it so you only have weeks to months worth of supply

30
Q

What is a “dual deficiency” (folate deficiency)

A

Caused by ETOH abuse

  • interferes w initial absorption
  • f’s with enterohepatic circulation
31
Q

Causes of folate deficiency?

A

Nutritional causes

Increased requirements (pregg)

Malabsorptive causes (rare but may be GI or drugs)

32
Q

What drugs are associated w B9 deficiency?

A

ETOH (its medicine, dont judge me)

Methotrexate
Sulfasalazine (ASA derivative)
Triamterene (K sparing diuretic)
Pyrimethamine (antiparasitic)
Trimethoprim/sulfam ethozazole
Diphenylhydatoin (phenytoin)
Barbituates
Topiramate
Hydroxyurea
33
Q

What is different about ETOH, topiramate, and hydroxyurea induced anemia?

A

They cause drug-induced macrocytic anemia with or without interfering w folate

34
Q

Clinical features of B12 and folate (list)

A 
Hematologic
Cardiopulmonary
GI
Derm
Genial 
Reproductive
Psych
NEUROPSYCHIATRIC (B12 specific)

See slide 29 for more in depth stuff

35
Q

One more time, what blood work is required for DX of megaloblastic anemias?

A 
Direct B12 and folate
- B12 <170pg/mL
- B9 < 150ng/mL
Homocysteine level
MMA
36
Q

Tx of asymptomatic B12 macrocytic anemia or b12 deficiency induced peripheral neuropathy

A

B12

PO: 1000mcg daily
Or
IM: 1000 mcg once monthly

If asymptomatic

37
Q

TX for perinicious anemia and neurological dysfunction?

A

You win shots for life (must be parenteral)

1000mcg IM daily x 1 week, then weekly x 4 weeks, then monthly x life

38
Q

Tx for neurologic dysfunction only

A

B12 - Can take PO once initial deficiency has been corected and pt is asymptomatic

Folate

39
Q

How fast do you see improvement when treating B12?

A

Erythropoiesis starts to normalize w/in 1-2 days

Hypersegmented neutrophils get better in 10-14 days

40
Q

How to treat folate deficiency?

A

Oral B9

1mg PO daily x 1-4 months or until mo-better

41
Q

Why does liver disease cause macrocytic anemia?

A

It impairs lipid metabolism

- we think excess lipids are deposited in RBC lipid bilayer resulting in increased size (macrocytosis)

42
Q

Beside absorption why does ETOH cause macrocytic anemia?

A

Direct bone marrow toxicity

Abnormal RBC lipid metabolism (like liver disease)

Interferes w folate metabolism

43
Q

Will alcohol induced macrocytic anemia get better?

A

Usually w/in 2-4 months of abstinence if irreversible damage has not occurred

44
Q

Myelodysplastic syndrome s (MDS) is aka?

A

Pre-leukemia

45
Q

What is myelodysplastic syndrome (MDS)?

A

Heterogeneous bone marrow disorders characterized by ineffective blood cell production and dysplasia due to mutation in a hematopoietic stem cell

46
Q

What causes MDS?

A

Primary: idiopathic

Secondary: med treatments

  • chemo
  • radiation therapy
  • toxic substances (benzene)
47
Q

MDS clinical features?

A
  • Hematologic (MCV 105+) (cytopenias)
  • increased risk of AML (leukemia) (roughly 30% get this)
  • present w fatigue, infection or bleeding
  • indolent presentation (wasting, fever)
  • +/- splenomegaly
48
Q

MDS diagnosis?

A

Cytopenia w hypercellular bone marrow

Morphologic abnormalities in 2 or more hematopoietic cell lines

Get a bone marrow biopsy

49
Q

MDS tx?

A

No single therapy

  • transfusions
  • hematologic stimulating factors
  • bone marrow transplant
  • experimental shit (chemo, immunosuppression etc)
50
Q

Marked reticulocytosis?

A

MCV spuriously increased when there are excessive reticulocytes in the peripheral blood. Usually transiently observed in patients with massive hemolysis without a coexisting microcytic process

51
Q

Hypothyroidism?

A

Mechanisms unknown.

Hypothyroid patients should also be evaluated for pernicious anemia due to chronic autoimmune thyroiditis

52
Q

Pregnancy for other macrocytic ?

A

INCREASED folate requirements may account for mild macrocytosis which is rarely OVer 100. Folate supplementaiton during pregnancy also significantly reduces risk of neural tube defects in child.

53
Q

Um, no mr vance

A

AB caffeinated is not a blood type

Senior - Heme-Onc (6 decks)

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